2.1. In vivo NMR Imaging General Considerations
Nuclear magnetic resonance (NMR) is now widely used for obtaining spatial images of human subjects for clinical diagnosis. Clinical usage of NMR imaging, also called magnetic resonance imaging or, simply, MRI, for diagnostic purposes has been reviewed [see e.g., Pykett, et al., Nuclear Magnetic Resonance, pgs. 157-167 (April, 1982) and T. F. Budinger, et al., Science, pgs. 288-298, (October, 1984)]. Several advantages of using such a procedure over currently used diagnostic methods, e.g., X-ray computer-aided tomography (CT), are generally recognized. For instance, the magnetic fields utilized in a clinical NMR scan are not considered to possess any deleterious effects to human health (see Budinger, supra., at 296). Additionally, while X-ray CT images are formed from the observation of a single parameter, X-ray attenuation, NMR images are a composite of the effects of number of parameters which are analyzed and combined by computer. Choice of the appropriate instrument parameters such as radio frequency (Rf), pulsing and timing can be utilized to enhance (or, conversely, attenuate) the signals of any of the image-producing parameters thereby improving the image quality and providing better anatomical and functional information. Finally, the use of such imaging has, in some cases, proven to be a valuable diagnostic tool as normal and diseased tissue, by virtue of their possessing different parameter values, can be differentiated in the image.
In MRI, the in vivo image of an organ or tissue is obtained by placing a subject in a strong external magnetic field and observing the effect of this field on the magnetic properties of the protons (hydrogen nuclei) of the water contained in and surrounding the organ or tissue. A number of parameters can be measured, but the proton relaxation times, T.sub.1 and T.sub.2, are of primary importance. T.sub.1 (also called the spin-lattice or longitudinal relaxation time) and T.sub.2 (also called the spin-spin or transverse relaxation time) depend on the chemical and physical environment of organ or tissue water and are measured using Rf pulsing technique; this information is analyzed as a function of distance by computer which then uses it to generate an image.
The image produced, however, often lacks definition and clarity due to the similarity of the signal from other tissues. In many cases, this eliminates any diagnostic effectiveness, as any signal differences between normal and diseased tissue are ordinarily small. To overcome this drawback, researchers have tried increasing the external magnetic field intensity of the scanning instruments and the use of contrast agents. Increasing the external magnetic field intensity appears to be of limited utility because higher Rf frequencies are used (since the resonant frequency, which is proportional to the external field intensity, is higher) and as this frequency is increased, the depth to which it can penetrate through tissue decreases. Thus, the use of contrast agents appears to be the most promising avenue to pursue.